EXERCISE MODALITY AND METABOLIC STATUS DRIVE DISTINCT LIPIDOMIC RESPONSES AFTER ACUTE AEROBIC, RESISTANCE AND COMBINED TRAINING

Lipid metabolism is significantly altered in obesity and type 2 diabetes (T2D) and is modulated by exercise modality, intensity, and duration. While high-intensity aerobic training (AT) and resistance training (RT) have been shown to modify metabolic profiles, the acute lipidomic response to moderate-intensity exercise, particularly in individuals with metabolic disorders, remains unclear. This study used high-resolution direct-infusion mass spectrometry (DIMS) lipidomics to investigate the acute lipidomic responses to AT, RT, and combined training (CT) in individuals with normal weight (NW), obesity (OB), and T2D. A randomised crossover design was employed, with 57 individuals (18 NW, 22 OB, 17 T2D) undergoing three supervised training sessions (AT, RT, CT). Blood samples were collected pre-, post-, 30 min and 60 min post-exercise and lipidomic profiles were assessed using untargeted direct infusion–high-resolution mass spectrometry (DI-HRMS). NW individuals showed the most dynamic responses, particularly in glycerophospholipids (GP) and sphingolipids (SP), reflecting greater insulin sensitivity. OB and T2D groups showed delayed lipid recovery, with prolonged elevated levels of triacylglycerols (TAGs), diacylglycerols (DAGs), and ceramides (Cers), indicative of insulin resistance (IR), and metabolic inflexibility. RT and CT were more effective than AT in reducing pro-inflammatory lipids, such as DAG, ganglioside GM3 and Cer. Hierarchical clustering analysis (HCA) further revealed distinct lipid regulation patterns and lipid class-specific cluster enrichment, modulated by both exercise and metabolic phenotype. These findings highlight importance of personalised exercise prescriptions, particularly those incorporating resistance components, have the potential to optimise metabolic responses and enhance lipid metabolism in individuals with IR.